Preparation of Heteroaromatic Derivatives

Several new routes to furans and to pyrroles have recently been put forward.
Inspired by the Achmatowicz ring expansion, Patrick J. Walsh of the University
of Pennsylvania developed (J. Am. Chem. Soc.2008, 130,
4097.
)
the
oxidative rearrangement of 3-hydroxalkyl furans such as 1 to the
3-aldehyde 2. José M. Aurrecoechea of the Universidad del País Vasco
established (J. Org. Chem.2008, 73, 3650.
)
that
cumulated alcohols, available by reduction of alkynes such as 3 with SmI2,
rearrange under Pd catalysis, and then add to an acceptor alkene such as 4,
to give the furan 5. Vladimir Gevorgyan of the University of Illinois at
Chicago used (J. Am. Chem. Soc.2008, 130, 1440.
)
an Au
catalyst to rearrange an allene such as 6 to the bromo furan 7.
Fabien L. Gagosz of the Ecole Polytechnique, Palaiseau, also found (Org. Lett.2007, 9, 3181.
)
that an
Au catalyst rearranged the eneyne 8 to the pyrrole 9.

Azido esters such as 10 are readily prepared from the corresponding
aldehyde by phosphonate condensation. Shunsuke Chiba and Koichi Narasaka of
Nanyang Technology University demonstrated (Org. Lett.2008, 10,
313.
)
that
thermal condensation of 10 with acetyl acetone 11 gave the pyrrole
12, while Cu catalyzed condensation with acetoacetate 13 gave the
complementary pyrrole 14.

Huan-Feng Jiang of South China University of Technology observed (Tetrahedron
Lett.2008, 49, 3805.
)
that condensation of an acid chloride 15 with an alkyne 16,
presumably to give the alkynyl ketone, followed by the addition of hydrazine
delivered the pyrazole 17. Masanobu Uchiyama of RIKEN and Florence Mongin
of the Université de Rennes 1 established (J. Org. Chem.2008,
73, 177.
)
that a pre-formed pyrazole 18 could be metalated and then
iodinated, to give 19. Xiaohu Deng of Johnson & Johnson, San Diego
reported (Org. Lett.2008, 10, 1307,
;
J.
Org. Chem.2008, 73, 2412,
)
complementary routes to pyrazoles, combining 20 and 21 under
acidic conditions to give 22, and under basic conditions to give 23.

Mark Lautens of the University of Toronto demonstrated (J. Org. Chem.2008, 73, 538.
)
that
dibromoalkenes such as 24, readily available from the corresponding
aldehyde, could be condensed with an organoborane such as 25 to give the
indole 26. Tao Pei and Cheng-yi Chen of Merck Process established (Angew.
Chem. Int. Ed.2008, 47, 4231.
)
that
the addition of an organometallic to the ketone 27 drove rearrangement to
a homologated ketone, that on acid work-up gave the indole 28.

Each of these approaches depended on the availability of the ortho-substituted
aniline starting materials. Junbiao Chang and Kang Zhao of Tianjin University
devised (J. Org. Chem.2008, 73, 2007.
)
a complementary
approach, the cyclization of 29 to 30, in the process directly
aminating the benzene ring. Marijan Kocevar of the University of Ljubljana
established (Tetrahedron2008, 64, 45.
)
an alternative Diels-Alder approach to indoles, combining 31 and 32
to give 33.

The preparation of pyridines will be covered in the next column on
heteroaromatic construction.